title: Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events.
abstract: The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10(-5)) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.
authors.affiliation: 1] Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands [2] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Leusink
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: N C
authors.initials: NC
authors.lastname: Onland-Moret
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: F W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Global Epidemiology, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Ding
authors.affiliation: Assistance Publique-Hopitaux de Paris, Hopital St. Antoine, URC-EST, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Kotti
authors.affiliation: Centre for Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: N R
authors.initials: NR
authors.lastname: van Zuydam
authors.affiliation: Program in Pharmacogenomics, Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Papp
authors.affiliation: 1] Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France [2] Universite Paris-Descartes, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Danchin
authors.affiliation: Centre for Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: L
authors.initials: L
authors.lastname: Donnelly
authors.affiliation: Centre for Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Morris
authors.affiliation: 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA [2] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P A F M
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: O H
authors.initials: OH
authors.lastname: Klungel
authors.affiliation: 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA [2] Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: van Gilst
authors.affiliation: 1] Assistance Publique-Hopitaux de Paris, Hopital St. Antoine, URC-EST, Paris, France [2] Department of Clinical Pharmacology, Universite Pierre et Marie Curie (Paris 6), Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Simon
authors.affiliation: 1] Global Epidemiology, AstraZeneca R&D, Mölndal, Sweden [2] Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: Centre for Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: C N A
authors.initials: CN
authors.lastname: Palmer
authors.affiliation: Program in Pharmacogenomics, Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: W
authors.initials: W
authors.lastname: Sadee
authors.affiliation: 1] Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands [2] Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: 1] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands [2] Harvard Medical School, Boston, Massachusetts, USA [3] Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: de Boer
authors.affiliation: 1] Assistance Publique-Hopitaux de Paris, Hopital Bicetre, Service de Genetique Moleculaire, Pharmacogenetique et Hormonologie, Le Kremlin Bicetre, France [2] Universite Paris-Sud, Le Kremlin-Bicetre, France.
authors.forename: C
authors.initials: C
authors.lastname: Verstuyft
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D044465:White People
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol